This proposal is for an integrated biochemical, cell biological, and anatomical study of fibronectin (FN) and its role in inflammatory lung injury. FN, a component of extracellular matrix and plasma, mediates cell adhesion and interaction with collage and other components of the extracellular matrix. FN is a sensitive target of leukocyte proteases in vitro, and is cleaved by leukoctye elastase to biologically active peptide fragments which may compete with intact FN for binding to cells or collagen. Emphasis is placed upon in vitro models to assess the biological impact of collagen binding and cell adhesive peptides upon FN interaction with cells and collagen. Purified peptides or antisera against these peptides will be used also as probes to study FN mediated cell adhesion and interaction with collagen in vitro. Methods will be developed for specific, sensitive detection of FN degradation products and ultrastructural localization of FN in cells and tissue. The methods developed in vitro will be applied in two in vivo animal models of lung injury with different pathophysiologic consequences, leukocyte elastase induced emphysema and bleomycin induced fibrosis. In these models, we will assess degradation of FN, the effects of lung injury fibrosis. In these models, we will assess degradation of FN, the effects of lung injury upon FN structure and distribution, and transudation of FN into the injured alveolus.